Reprogenetic News Roundup #14

Gene editing & enhancement, PRS in cardiovascular prevention, declining births in Nordics, lowest fertility ever in Canada, genetic "butterfly effect" & autism

Welcome to the latest issue of the Reprogenetic News Roundup! Highlights from this week’s edition:

• Repro/genetics

  • Debate on human enhancement and germline genome editing in Singapore

  • NHS study shows polygenic risk scores can be used in prevention of cardiovascular disseases

• Population policies & trends

  • The FT reports on falling birth rates in the Nordics

  • StatCan: Canada hits lowest fertility on record of 1.33 per woman

• Genetic Studies

  • Genetic butterfly effect shapes autism risk

• Further Learning

Repro/genetics

Should Singapore embrace human enhancement via germline genome editing? (Bioedge)

• Dr. Alexis Heng, associate professor of biomedical science at Peking University, argues in an op-ed against human enhancement via germline genome editing.

• Recent years have witnessed the emergence of a “New Eugenics” movement by people highly-educated technopreneurs and white-collar professionals in Western countries, who believe that it is their natural right (based on individual reproductive autonomy) to screen, select or genetically engineer non disease-related socially-desirable traits in their offspring, such as high IQ and athletic prowess.

• “Procreative beneficence” holds that parents have significant moral reasons to select, of the possible children they could have, the child who is most likely to experience the greatest well-being – that is, the most advantaged child, the child with the best chance at having the best life.

• Many “new eugenicists” believe they are being socially responsible by not only committing to reproduce prolifically to compensate for declining birthrates in their respective countries, but also by enabling the world to be increasingly populated by their “genetically superior” offspring, who will lead longer, healthier, better and more fulfilling lives, and contribute more to the advancement of human civilization through their superior intellect.

• Dr. Heng suggests such sentiments may be more motivated by personal and upper middle-class egoism and narcissism.

• The most prominent proponent of pro-natalism is the billionaire Elon Musk. He currently has 11 children by three different women, most of whom were artificially conceived by IVF.

• In doing so, Musk has said he is “Doing my best to help the underpopulation crisis. Population collapse due to low birth rates is a much bigger risk to civilization than global warming.”

• Dr. Heng fears such thinking could have negative effects in East-Asian Confucian societies such as Singapore, which are hyper-competitive and obsessed with material success, social status and academic excellence.

• Ultra-low fertility in East Asia, with most families having only one child due to high living costs and educational stress, may motivate prospective parents to use new assisted reproductive technologies to beget children with the “best” or “most optimal” genetics, rather than leaving it to chance via the natural fertilization.

• Indigenous movements favoring genetic enhancement have emerged in East Asia. The “uterine morality” (zigong daode) movement in mainland China amongst feminists argues that because women bear the brunt of birthing and caring for children, they should only accept only the very best genetic material into their wombs. These argue prospective mothers must take responsibility for her future children by selecting a good-looking, intelligent, strong, financially-sound man with no family history of genetic disorders, so as to ensure that future generations evolve into healthy, beautiful, and intelligent beings.

• Dr. Heng argues that if Singapore were to embrace germline genome editing for human enhancement, this could have negative consequences such as damaging Singapore’s reputation, increasing social inequality, and create unrealistic expectation of gene-edited children.

Genomics plc publishes results showing successful use of polygenic risk scores for cardiovascular disease in NHS primary care (yahoo!finance)

• Genomics plc, a healthcare company aiming to transform health through the power of genomics, has conducted the first clinical trial investigating the use of polygenic risk scores (PRS) to support the prevention of cardiovascular disease in Britain’s National Health Service (NHS).

• The study was conducted as part of Genomics’ HEART study (Healthcare Evaluation of Absolute Risk Testing) and published in the European Journal of Preventive Cardiology.

• Many people at high genetic risk of certain diseases remain invisible to the NHS.

• The HEART study showed the feasibility of incorporating a tool combining genetic and non-genetic risk factors for cardiovascular diseases into routine primary care.

• The paper shows genetic information adds value to doctors’ clinical decision-making. In the study, doctors reported they would change their management of 13.1% of the overall study population, as a result of knowing their integrated risk.

• Professor Sir Peter Donnelly, Founder and Chief Executive Officer of Genomics plc, said: “Genetics is a critical risk factor for many of the most common diseases, and the HEART study has shown that its use in the prevention of cardiovascular disease fits well with standard clinical workflows, is very well received by patients, and significantly impacts their clinical management. We hope that it will also encourage similar studies incorporating genetics into clinical risk prediction for other common diseases.”

• Ahmet Fuat, Chief Investigator HEART and Honorary Professor of Primary Care Cardiology at Durham University said: “Prevention is at the heart of what we do as GPs and risk assessment underpins that. We have shown in HEART that genomic testing improves how we identify those patients who most need preventative measures, closer management, and treatment, and helps us target the right interventions for them. I changed my management of a number of my patients directly due to the new information coming through from the integrated tool. Some patients who had been reluctant to start statin therapy, for example, became keen to take them when the new risk scores came through. We could not show it in a short study like this, but I believe this approach of integrating genetic information into routine best practices could save lives and be a game-changer for patients and GPs.”

Population Policies & Trends

Birth rates are falling in the Nordics. Are family-friendly policies no longer enough? (Financial Times)

• The Nordic countries’ family policies used to be a model for others seeking to reconcile high female labor force participation with sustainable fertility.

• Finland’s fertility rate has fallen nearly a third since 2010. It is now below the UK’s, where the social safety net is more limited, and only slightly above Italy’s, where traditional gender roles persevere.

• Across the world, fertility is declining in very different societies — conservative and liberal, big and small state, growing economies and stagnating ones.

• In Europe in 2023, the rate fell in “Hungary, Germany, Iceland, Ireland, all the ones who were really high or were paraded as examples . . . It seems that Finland might be a forerunner, unfortunately,” said Anna Rotkirch, research director at the Family Federation of Finland’s Population Research Institute, who has advised then Finnish Prime Minister Sanna Marin on boosting fertility.

• Italian Prime Minister Giorgia Meloni, has said the birth rate is a “top priority”. French President Emmanuel Macron this month promised “demographic rearmament”.

• Rotkirch cautions that their efforts are likely to underwhelm: “When you work with politicians, you always see the same things. ‘Oh yes, we should have one month’s more paternity leave!’ All the scholars are like: you should, but it won’t change anything.”

• There is a risk Europe will fall into the pattern of ultra-low fertility witnessed in East Asian contries.

• “The strange thing with fertility is nobody really knows what’s going on. The policy responses are untried because it’s a new situation. It’s not primarily driven by economics or family policies. It’s something cultural, psychological, biological, cognitive,” said Rotkirch.

• Rotkirch’s research suggests children do not fit into many millennials’ life plans: “In most societies, having children was a cornerstone of adulthood. Now it’s something you have if you already have everything else. It becomes the capstone.”

• This may explain why it is no longer Europeans with less education who want more children. Instead “those who are well-off in many ways — [who] have a partner, have support from their parents, are employed, are not lonely — want to have more children . . . This is quite a new thing in many countries, including England.”

• Rotkirch suspects the spread of social media is playing a role by stoking political polarisation, loneliness and mental health issues, which reduce fertility.

• Stabilising birth rates may require not just top-down policies but a societal rethink. Rotkirch: “What would society look like if we valued reproduction, and raising babies, not just your own, as much as [economic] production?”

• In Finland, three-quarters of the recent decline in fertility is attributable to people who have no children. Rotkirch: “You see similar trends everywhere.”

• In family barometer surveys among Finns born in the late 1970s and 1980s, fewer than 1/20 25-year-olds said they didn’t want to have children. Among those born in the late 1980s and early 1990s, that proportion rose to nearly 1/4.

• Nearly 40% of Finnish men with low education are now childless at the age of 45. Most have no partners. Men are as likely as women to say they want children, but are more likely to be childless.

• “It’s OK to say I don’t like children, and it’s the only demographic you can ever say that about,” said Rotkirch. When she asked her students to guess the results of surveys of parents, they wildly underestimated how satisfied the parents were — including with their relationships and their ability to take care of their kids.

• In her 2021 policy guidelines for the Finnish government, Rotkirch wrote that the “goal should be to restore the birth rate to 1.6 in the short term and 1.8 in the longer term”. Instead the rate fell further — to 1.27 in 2023.

• Rotkirch is exasperated by those who think lower fertility rates should be welcome, given climate change. “Climate change has to be combated now, and if you look at fertility changes, they are long term.”

• Nor can immigration simply fill the gap. “There are many good reasons not to have kids, but importing Filipino workers, who leave their children behind, is seriously not the answer.”

• In one survey, 11% of Finnish women said Russia’s invasion of Ukraine made them less likely to have children.

• Rotkirch is not scared by the future, but she doesn’t want to live in a society of old, lonely people. “I think it’s sad if our way of living is living alone on the screens, in the flats, not having sex, not having stable partnerships, not having children.”

Fertility in Canada, 1921 to 2022 (Statistics Canada)

• In 2022, Canada’s total fertility rate (TFR) reached its lowest level on record, at 1.33 children per woman.

• Most (10 out of 13) provinces and territories saw their TFR reach a record low in 2022.

• The decrease in the TFR from 2021 to 2022 (-7.4%) is the largest decrease since 1971 to 1972 (-7.6%), at the height of the “baby bust” that followed the baby boom (1946 to 1965).

• Apart from the United States, all G7 countries experienced a fertility decline between 2021 and 2022. Canada’s decrease was one of the largest among high-income countries.

• Over the period from 1921 to 2022, the lowest TFRs occurred in the last five years: 2022 (1.33), 2020 (1.41), 2021 (1.44), 2019 (1.47) and 2018 (1.51).

• From 2021 to 2022, fertility rates decreased in all age groups of women less than 40.

• Following a period of slow and steady decrease from 2009 to 2019, Canada’s TFR was relatively volatile from 2020 to 2022, with an initial large downward swing, then an increase, followed by another drop. This pattern runs in parallel with the experience of many other countries over the same period, suggesting the COVID-19 pandemic may have temporarily disrupted fertility behaviours.

• The average age of mothers at childbirth has been increasing without interruption for nearly five decades, from 26.7 years in 1976 to 31.6 years in 2022.

More on population policies & trends:

• “Global sperm counts have declined 52% since 1970 with the majority of decline in Western countries” (Medium/Homeless Romantic)

• Professor Darel E. Paul: “Reviving fertility might require a cultural revolution” (Fusion)

• How the population crunch ends (Futurist Letters)

• “Three basic facts that affect fertility (Virginia’s Newsletter)

• “Fertility and culture: a deep dive” (@MoreBirths)

Genetic Studies

“Genomic ‘butterfly effect’ shapes autism risk in ‘largest’ autism spectrum disorder study (Interesting Engineering)

• Scientists from the RIKEN Center for Brain Sciences (CBS) have discovered autism spectrum disorder (ASD) may be caused by genes causing a kind of “butterfly effect” on surrounding genes.

• Recent studies have shown that the high degree of heritability of autism cannot be explained solely by examining genome areas that codes for proteins, but may lie in the non-coding regions of the genome, particularly in promoters, which control whether or not proteins are produced.

• Atsushi Takata and his team at RIKEN CBS examined new mutations in these non-coding regions of the genome with one of the world’s largest GWAS on autism to date, analyzing a vast dataset of over 5,000 families.

• The study found new mutations in promoters increased the risk of ASD only when these are in areas located in a topologically-associated domain (TAD), a self-interacting three-dimensional genomic region, containing ASD-related genes.

• The researchers confirmed their findings by using the CRISPR/Cas9 system to edit the DNA of stem cells. They made mutations in specific promoters and observed that a single genetic change in a promoter caused alterations in an ASD-associated gene within the same TAD.

• “At the very least, when assessing an individual’s risk for ASD, we now know that we need to look beyond ASD-related genes when doing a genetic risk assessment and focus on whole TADs that contain ASD-related genes,” explains Takata. “Further, an intervention that corrects aberrant promoter-enhancer interactions caused by a promotor mutation may also have therapeutic effects on ASD.”

• “By expanding our research, we will gain a better understanding of the genetic architecture and biology of ASD, leading to clinical management that enhances the well-being of affected individuals, their families, and society,” says Takata.

• The study was published in Cell Genomics.

More on genetic studies:

• “New software spots disease-causing genes with higher accuracy” (Interesting Engineering)

• “Asia’s largest scleroderma whole-genome association analysis” (Riken, Japan)

• “Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people” (Science Advances)

• “A genome-wide association study reveals the relationship between human genetic variation and the nasal microbiome” (Communications Biology)

• “The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study” (Cardiovascular Diabetology)

• “New genetic variants, trait associations uncovered with Chinese birth cohort sequences” (genomeweb)

• “Bonn researchers identify new risk locus in the genome for ACE inhibitor-induced angioedema” (University of Bonn)

Further Learning

• Why evolution has made weight loss so hard for humans (CNN Chasing Life podcast)

• “Why do some people readily believe climate scientists but reject the view of crop geneticists? Austrian survey provides some clues” (Genetic Choice Project/Profil)

• “Dreaming may have evolved as a strategy for co-operative survival” (PsyPost)

• “Parts of primate DNA unchanged for 65 million years, study finds” (The Hindu)

• “Scans of 10,000 brains show dramatic memory benefits from just 4 minutes of daily exercise” (Genetic Choice Project/Washington Post)

• After long importing genetically-modified crops, China expanding domestic production (SaskToday)

Disclaimer: The Genetic Choice Project makes every effort to include only reputable and relevant news, studies, and analysis on reprogenetics. We cannot fact-check the linked-to stories and studies, nor do the views expressed necessarily reflect those of the Genetic Choice Project.